Mutagenetix > Incidental Mutation

Incidental Mutation 'R3833:Med12'

275516

Institutional Source

Beutler Lab

Gene Symbol

Med12

Ensembl Gene

ENSMUSG00000079487

Gene Name

mediator complex subunit 12

Synonyms

Tnrc11, Mopa, OPA-1, Trap230

MMRRC Submission

040888-MU

Accession Numbers

Essential gene?

Essential (E-score: 1.000) question?

Stock #

R3833 (G1)

Quality Score

222

Status

Validated

Chromosome

Chromosomal Location

100317636-100341071 bp(+) (GRCm39)

Type of Mutation

missense

DNA Base Change (assembly)

C to A at 100339498 bp (GRCm39)

Zygosity

Heterozygous

Amino Acid Change

Proline to Glutamine at position 2037 (P2037Q)

Ref Sequence

ENSEMBL: ENSMUSP00000112729 (fasta)

Gene Model

predicted gene model for transcript(s): [ENSMUST00000065858] [ENSMUST00000087948] [ENSMUST00000087956] [ENSMUST00000117203] [ENSMUST00000117706] [ENSMUST00000118111] [ENSMUST00000151528] [ENSMUST00000130555]

AlphaFold

A2AGH6

Predicted Effect

probably benign
Transcript: ENSMUST00000065858

SMART Domains

Protein: ENSMUSP00000066304
Gene: ENSMUSG00000031302

Domain	Start	End	E-Value	Type
Pfam:COesterase	16	601	2.3e-194	PFAM
Pfam:Abhydrolase_3	180	342	1.7e-7	PFAM
transmembrane domain	685	707	N/A	INTRINSIC

Predicted Effect

possibly damaging
Transcript: ENSMUST00000087948
AA Change: P2037Q

PolyPhen 2 Score 0.491 (Sensitivity: 0.88; Specificity: 0.90)

SMART Domains

Protein: ENSMUSP00000085260
Gene: ENSMUSG00000079487
AA Change: P2037Q

Domain	Start	End	E-Value	Type
Med12	101	161	2.98e-24	SMART
low complexity region	273	282	N/A	INTRINSIC
Pfam:Med12-LCEWAV	287	758	1.5e-184	PFAM
low complexity region	1220	1231	N/A	INTRINSIC
low complexity region	1245	1267	N/A	INTRINSIC
low complexity region	1394	1412	N/A	INTRINSIC
low complexity region	1469	1480	N/A	INTRINSIC
low complexity region	1732	1774	N/A	INTRINSIC
low complexity region	1780	1794	N/A	INTRINSIC
Pfam:Med12-PQL	1821	2024	1.2e-79	PFAM
SCOP:d1bg1a1	2056	2129	3e-4	SMART

Predicted Effect

probably benign
Transcript: ENSMUST00000087956
AA Change: P2016Q

PolyPhen 2 Score 0.425 (Sensitivity: 0.89; Specificity: 0.90)

SMART Domains

Protein: ENSMUSP00000085269
Gene: ENSMUSG00000079487
AA Change: P2016Q

Domain	Start	End	E-Value	Type
Med12	101	161	2.98e-24	SMART
low complexity region	273	282	N/A	INTRINSIC
Pfam:Med12-LCEWAV	286	758	1.8e-213	PFAM
low complexity region	1220	1231	N/A	INTRINSIC
low complexity region	1245	1267	N/A	INTRINSIC
low complexity region	1394	1412	N/A	INTRINSIC
low complexity region	1469	1480	N/A	INTRINSIC
low complexity region	1732	1774	N/A	INTRINSIC
low complexity region	1780	1794	N/A	INTRINSIC
Pfam:Med12-PQL	1819	1970	1.5e-57	PFAM
Pfam:Med12-PQL	1968	2004	5.7e-18	PFAM
SCOP:d1bg1a1	2035	2108	4e-4	SMART

Predicted Effect

noncoding transcript
Transcript: ENSMUST00000113671

Predicted Effect

possibly damaging
Transcript: ENSMUST00000117203
AA Change: P2037Q

PolyPhen 2 Score 0.491 (Sensitivity: 0.88; Specificity: 0.90)

SMART Domains

Protein: ENSMUSP00000112729
Gene: ENSMUSG00000079487
AA Change: P2037Q

Domain	Start	End	E-Value	Type
Med12	101	161	2.98e-24	SMART
low complexity region	273	282	N/A	INTRINSIC
Pfam:Med12-LCEWAV	286	758	3.8e-214	PFAM
low complexity region	1220	1231	N/A	INTRINSIC
low complexity region	1245	1267	N/A	INTRINSIC
low complexity region	1394	1412	N/A	INTRINSIC
low complexity region	1469	1480	N/A	INTRINSIC
low complexity region	1732	1774	N/A	INTRINSIC
low complexity region	1780	1794	N/A	INTRINSIC
Pfam:Med12-PQL	1819	2025	1.5e-100	PFAM
SCOP:d1lsha3	2048	2107	4e-4	SMART

Predicted Effect

probably benign
Transcript: ENSMUST00000117706
AA Change: P2012Q

PolyPhen 2 Score 0.006 (Sensitivity: 0.97; Specificity: 0.75)

SMART Domains

Protein: ENSMUSP00000112852
Gene: ENSMUSG00000079487
AA Change: P2012Q

Domain	Start	End	E-Value	Type
Med12	101	161	2.98e-24	SMART
low complexity region	273	282	N/A	INTRINSIC
Pfam:Med12-LCEWAV	286	758	3.7e-214	PFAM
low complexity region	1220	1231	N/A	INTRINSIC
low complexity region	1245	1267	N/A	INTRINSIC
low complexity region	1394	1412	N/A	INTRINSIC
low complexity region	1469	1480	N/A	INTRINSIC
low complexity region	1732	1774	N/A	INTRINSIC
low complexity region	1780	1794	N/A	INTRINSIC
Pfam:Med12-PQL	1819	1966	7.5e-63	PFAM
Pfam:Med12-PQL	1964	2000	1.1e-18	PFAM
SCOP:d1lsha3	2023	2082	4e-4	SMART

Predicted Effect

probably benign
Transcript: ENSMUST00000118111

SMART Domains

Protein: ENSMUSP00000113863
Gene: ENSMUSG00000031302

Domain	Start	End	E-Value	Type
Pfam:COesterase	3	487	3.6e-161	PFAM
Pfam:Abhydrolase_3	66	232	2.4e-7	PFAM
transmembrane domain	571	593	N/A	INTRINSIC

Predicted Effect

noncoding transcript
Transcript: ENSMUST00000132269

Predicted Effect

noncoding transcript
Transcript: ENSMUST00000148846

Predicted Effect

noncoding transcript
Transcript: ENSMUST00000147443

Predicted Effect

noncoding transcript
Transcript: ENSMUST00000137664

Predicted Effect

probably benign
Transcript: ENSMUST00000151528

SMART Domains

Protein: ENSMUSP00000123283
Gene: ENSMUSG00000031302

Domain	Start	End	E-Value	Type
Pfam:COesterase	16	621	3.4e-207	PFAM
Pfam:Abhydrolase_3	200	363	1.2e-6	PFAM
transmembrane domain	705	727	N/A	INTRINSIC

Predicted Effect

probably benign
Transcript: ENSMUST00000130555

SMART Domains

Protein: ENSMUSP00000122213
Gene: ENSMUSG00000031302

Domain	Start	End	E-Value	Type
Pfam:COesterase	16	510	4.6e-179	PFAM
Pfam:Abhydrolase_3	160	323	1.5e-7	PFAM

Meta Mutation Damage Score

0.0732

Coding Region Coverage

1x: 99.3%
3x: 98.7%
10x: 97.7%
20x: 96.4%

Validation Efficiency

97% (70/72)

MGI Phenotype

FUNCTION: [Summary is not available for the mouse gene. This summary is for the human ortholog.] The initiation of transcription is controlled in part by a large protein assembly known as the preinitiation complex. A component of this preinitiation complex is a 1.2 MDa protein aggregate called Mediator. This Mediator component binds with a CDK8 subcomplex which contains the protein encoded by this gene, mediator complex subunit 12 (MED12), along with MED13, CDK8 kinase, and cyclin C. The CDK8 subcomplex modulates Mediator-polymerase II interactions and thereby regulates transcription initiation and reinitation rates. The MED12 protein is essential for activating CDK8 kinase. Defects in this gene cause X-linked Opitz-Kaveggia syndrome, also known as FG syndrome, and Lujan-Fryns syndrome. [provided by RefSeq, Aug 2009]
PHENOTYPE: Male chimeras hemizygous for a null allele arrest at E7.5 and lack anterior visceral endoderm. Male chimeras hemizygous for a hypomorphic allele die at E10.5 showing failure of neural crest cell migration and severe defects in neural tube closure, axis elongation, somitogenesis and heart formation. [provided by MGI curators]

Allele List at MGI

Other mutations in this stock

Total: 73 list
Gene	Ref	Var	Chr/Loc	Mutation	Predicted Effect	Zygosity
9630041A04Rik	G	A	9: 101,820,062 (GRCm39)	G161S	probably damaging	Het
Acp7	T	C	7: 28,314,519 (GRCm39)	D282G	probably benign	Het
Atp10d	T	A	5: 72,396,568 (GRCm39)	C258S	possibly damaging	Het
Atp6ap1	T	C	X: 73,340,813 (GRCm39)	I10T	possibly damaging	Het
Atp6v0d2	T	G	4: 19,922,395 (GRCm39)	N35H	probably damaging	Het
Bcat1	T	A	6: 144,955,834 (GRCm39)	D349V	probably damaging	Het
Cacnb2	A	T	2: 14,986,236 (GRCm39)	I338F	probably damaging	Het
Ccn6	T	C	10: 39,030,945 (GRCm39)	K193E	probably benign	Het
Ccr1	T	C	9: 123,764,324 (GRCm39)	T69A	possibly damaging	Het
Cenpe	T	G	3: 134,928,083 (GRCm39)		probably benign	Het
Cps1	G	A	1: 67,178,946 (GRCm39)	G53R	probably damaging	Het
Cstb	T	C	10: 78,263,184 (GRCm39)	F70L	probably benign	Het
Cyb5d2	G	T	11: 72,686,349 (GRCm39)	S80R	possibly damaging	Het
Cyfip2	T	C	11: 46,152,333 (GRCm39)	D485G	probably benign	Het
Cyp27b1	G	T	10: 126,886,929 (GRCm39)	V382L	probably damaging	Het
Cyp8b1	C	A	9: 121,745,109 (GRCm39)	Q74H	probably benign	Het
Dennd2a	G	A	6: 39,483,651 (GRCm39)	P403L	probably damaging	Het
Dennd2a	G	T	6: 39,483,657 (GRCm39)	S401Y	probably damaging	Het
Dnaaf5	T	C	5: 139,167,320 (GRCm39)	V447A	possibly damaging	Het
Dpp9	A	T	17: 56,506,113 (GRCm39)	F429I	possibly damaging	Het
Gcn1	A	T	5: 115,730,191 (GRCm39)	Q835L	probably benign	Het
Gtf2b	T	A	3: 142,477,153 (GRCm39)	D8E	probably benign	Het
Hao1	A	T	2: 134,364,925 (GRCm39)	V234D	probably damaging	Het
Hephl1	T	C	9: 14,981,044 (GRCm39)	E796G	probably damaging	Het
Herc4	A	G	10: 63,081,739 (GRCm39)	I21V	probably benign	Het
Htt	T	A	5: 34,979,062 (GRCm39)	V815D	probably benign	Het
Iglv2	A	T	16: 19,079,593 (GRCm39)	M1K	probably null	Het
Igsf8	G	T	1: 172,145,837 (GRCm39)	A315S	probably benign	Het
Il1a	T	C	2: 129,148,599 (GRCm39)	D37G	possibly damaging	Het
Iqcb1	T	A	16: 36,652,276 (GRCm39)	C62*	probably null	Het
Itgad	A	T	7: 127,785,405 (GRCm39)	T381S	probably damaging	Het
Itpkb	T	C	1: 180,161,260 (GRCm39)	V462A	probably benign	Het
Kalrn	T	A	16: 33,860,259 (GRCm39)	R199*	probably null	Het
Kif24	G	T	4: 41,395,064 (GRCm39)	A603D	probably damaging	Het
Kif26b	GAAA	GAA	1: 178,744,181 (GRCm39)		probably null	Het
Klrc3	A	G	6: 129,620,181 (GRCm39)	L24P	probably damaging	Het
Lmnb1	A	C	18: 56,861,598 (GRCm39)	D163A	probably benign	Het
Lrrc9	T	C	12: 72,529,765 (GRCm39)	L912P	probably damaging	Het
Mageh1	A	T	X: 151,820,004 (GRCm39)	W111R	probably damaging	Het
Mapk7	A	G	11: 61,380,680 (GRCm39)	S641P	possibly damaging	Het
Mapt	A	T	11: 104,177,961 (GRCm39)	Q38L	possibly damaging	Het
Med22	A	G	2: 26,800,379 (GRCm39)	S17P	probably damaging	Het
Mep1b	C	T	18: 21,219,296 (GRCm39)	T150I	possibly damaging	Het
Mroh1	C	T	15: 76,285,819 (GRCm39)	T71I	probably benign	Het
Nap1l3	A	G	X: 121,305,995 (GRCm39)	V241A	possibly damaging	Het
Pcdhga6	A	T	18: 37,841,479 (GRCm39)	N400Y	probably damaging	Het
Pdgfd	T	C	9: 6,359,762 (GRCm39)	S278P	probably damaging	Het
Pgap1	A	G	1: 54,596,624 (GRCm39)	M39T	probably damaging	Het
Pgc	C	A	17: 48,040,236 (GRCm39)	F93L	probably null	Het
Phf14	A	G	6: 11,933,873 (GRCm39)		probably null	Het
Piezo2	A	G	18: 63,214,733 (GRCm39)		probably null	Het
Pja2	T	C	17: 64,616,397 (GRCm39)	D166G	probably benign	Het
Ppp1r12c	T	A	7: 4,485,785 (GRCm39)		probably benign	Het
Pus3	G	C	9: 35,477,874 (GRCm39)	G369R	probably benign	Het
Rhbdf2	T	A	11: 116,495,250 (GRCm39)	D251V	probably damaging	Het
Rsad1	A	G	11: 94,434,130 (GRCm39)	V366A	probably benign	Het
S100a10	T	C	3: 93,471,680 (GRCm39)	V88A	probably damaging	Het
Scarf1	T	C	11: 75,406,078 (GRCm39)	C121R	probably damaging	Het
Scn7a	A	G	2: 66,528,028 (GRCm39)	S821P	probably damaging	Het
Sco1	T	C	11: 66,944,605 (GRCm39)	V76A	probably damaging	Het
Sdsl	C	A	5: 120,601,183 (GRCm39)	A30S	probably benign	Het
Slc26a6	C	T	9: 108,733,117 (GRCm39)	T32I	possibly damaging	Het
Slit3	A	T	11: 35,579,509 (GRCm39)	S1229C	probably null	Het
Snd1	G	T	6: 28,531,403 (GRCm39)		probably benign	Het
Tdrd3	A	G	14: 87,718,221 (GRCm39)	T201A	probably damaging	Het
Tekt1	T	C	11: 72,245,645 (GRCm39)	N170S	probably benign	Het
Thsd1	T	G	8: 22,733,132 (GRCm39)	S60A	possibly damaging	Het
Tmem121b	C	T	6: 120,469,841 (GRCm39)	G292E	probably damaging	Het
Trim63	A	G	4: 134,048,507 (GRCm39)	N172S	probably benign	Het
Usp24	T	C	4: 106,219,209 (GRCm39)		probably null	Het
Zdhhc16	T	A	19: 41,926,553 (GRCm39)		probably null	Het
Zfp1010	T	C	2: 176,956,998 (GRCm39)	S167G	possibly damaging	Het
Zfp709	G	A	8: 72,642,906 (GRCm39)	V112M	probably benign	Het

Other mutations in Med12

Allele	Source	Chr	Coord	Type	Predicted Effect	PPH Score
IGL00668:Med12	APN	X	100,324,792 (GRCm39)	missense	probably benign	0.02
IGL01122:Med12	APN	X	100,325,149 (GRCm39)	splice site	probably benign
IGL01331:Med12	APN	X	100,324,360 (GRCm39)	missense	possibly damaging	0.82
IGL01636:Med12	APN	X	100,318,795 (GRCm39)	missense	probably damaging	1.00
IGL02121:Med12	APN	X	100,331,948 (GRCm39)	splice site	probably benign
IGL02415:Med12	APN	X	100,325,396 (GRCm39)	missense	probably damaging	1.00
IGL02479:Med12	APN	X	100,340,598 (GRCm39)	unclassified	probably benign
IGL02597:Med12	APN	X	100,328,538 (GRCm39)	missense	probably damaging	1.00
IGL02904:Med12	APN	X	100,337,784 (GRCm39)	splice site	probably null
IGL03002:Med12	APN	X	100,339,461 (GRCm39)	missense	probably benign	0.00
IGL03006:Med12	APN	X	100,321,684 (GRCm39)	missense	probably damaging	1.00
IGL03366:Med12	APN	X	100,321,695 (GRCm39)	missense	probably benign	0.37
R3831:Med12	UTSW	X	100,339,498 (GRCm39)	missense	possibly damaging	0.49
Z1176:Med12	UTSW	X	100,337,179 (GRCm39)	missense	possibly damaging	0.95
Z1176:Med12	UTSW	X	100,324,831 (GRCm39)	missense	probably damaging	1.00

Predicted Primers

PCR Primer
(F):5'- CTCCTCTCATTAGTGCCAAGACG -3'
(R):5'- TCTGACACAATCCCATGGCC -3'

Sequencing Primer
(F):5'- CATTAGTGCCAAGACGAATGAATAC -3'
(R):5'- ATGGCCTTACCCGTAGCATCTG -3'

Posted On

2015-04-06